Oncograms Visualize Factors Influencing Long-Term Survival of Cancer Patients Treated with Adenoviral Oncolytic Immunotherapy

Abstract

The first US Food and Drug Administration (FDA)- and EMA-approved oncolytic virus has been available since 2015. However, there are no markers available that would predict benefit for the individual patient. During 2007–2012, we treated 290 patients with advanced chemotherapy-refractory cancers, using 10 different oncolytic adenoviruses. Treatments were given in a Finnish Medicines Agency (FIMEA)-regulated individualized patient treatment program (the Advanced Therapy Access Program [ATAP]), which required long-term follow-up of patients, which is presented here. Focusing on the longest surviving patients, some key clinical and biological features are presented as “oncograms.” Some key attributes that could be captured in the oncogram are suggested to predict treatment response and survival after oncolytic adenovirus treatment. The oncogram includes immunological laboratory parameters assessed in peripheral blood (leukocytes, neutrophil-to-lymphocyte ratio, interleukin-8 [IL-8], HMGB1, anti-viral neutralizing antibody status), features of the patient (gender, performance status), tumor features (histological tumor type, tumor load, region of metastases), and oncolytic virus-specific features (arming of the virus). The retrospective approach used here facilitates verification in a prospective controlled trial setting. To our knowledge, the oncogram is the first holistic attempt to identify the patients most likely to benefit from adenoviral oncolytic virotherapy.

RETRACTED: Long Noncoding RNA OIP5-AS1 Promotes the Progression of Liver Hepatocellular Carcinoma via Regulating the hsa-miR-26a-3p/EPHA2 Axis

“…[18][19][20] Much evidence shows that lncRNA is involved in many biological processes, such as cancer cell proliferation, apoptosis, invasion, and so on. [21][22][23][24][25][26] Moreover, because of their genome-wide expression patterns in a variety of tissues and their tissue specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for cancer. [27][28][29][30] lncRNA OIP5 antisense RNA 1 (OIP5-AS1), a prominent tumorassociated lncRNA, contributes to intricate cellular mechanisms during tumorigenesis and development of malignant tumors.…”

Oncolytic viruses for cancer immunotherapy

“…Between 2007 and 2012, 290 advanced cancer patients were treated with 10 different oncolytic viruses (Table 4) totaling 821 treatments. A long-term follow-up of these patients has been published [5]. Treatments were given in the context of an individualized treatment program under the EU Advanced Therapies directive [5].…”

“…A long-term follow-up of these patients has been published [5]. Treatments were given in the context of an individualized treatment program under the EU Advanced Therapies directive [5]. While many objective responses were seen, no definite conclusions regarding overall survival benefit can be drawn as no reliable control group was available.…”

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients

“…It is shown that overexpression of hsa-miR-497-5p can regulate the expression of Smad3 and lead to cell cycle arrest in the G0/G1 phase [25][26][27]. Overexpression of miR-497-5p can reduce the content of insulin receptors and induce insulin resistance in HFD-MES rats [28][29][30]. Furthermore, the expression of miR-497- hsa-miR-1258 hsa-miR-424-5p hsa-miR-139-3p hsa-miR-139-5p hsa-leHCC-7c-3p hsa-miR-511-5p hsa-miR-195-5p hsa-miR-326 hsa-miR-497 -5p hsa-miR-122 -3p hsa-leHCC-7c-5p hsa-miR-101-3p hsa-miR-30c-1-3p hsa-miR-125b-2-3p hsa-miR-99a-3p hsa-miR-130a-3p hsa-miR-29c-3p hsa-miR-378a-5p hsa-miR-24-1-5p hsa-miR-26b-3p hsa-miR-30e-3p hsa-miR-455-3p hsa-miR-125b-5p hsa-miR-26b-5p hsa-miR-99a-5p hsa-miR-378c hsa-miR-30a-3p hsa-miR-1295b-5p hsa-leHCC-7g-3p hsa-leHCC-7b-3p hsa-miR-29c-5p hsa-miR-505-3p hsa-miR-30c-2-3p hsa-miR-500b-3p hsa-miR-532-5p hsa-miR-501-3p hsa-miR-301a-3p hsa-miR-589-3p hsa-miR-222-3p hsa-miR-421 hsa-miR-19a-3p hsa-miR-500a-3p hsa-miR-501-5p hsa-miR-221-3p hsa-miR-589-5p hsa-miR-4326 hsa-miR-188-5p hsa-miR-1301-3p hsa-miR-219b-3p hsa-miR-93-5p hsa-miR-3677-3p hsa-miR-18a-5p hsa-miR-1180-3p hsa-miR-1226-3p hsa-miR-21-5p hsa-miR-877-5p hsa-miR-224-3p hsa-miR-760 hsa-miR-4661-5p hsa-miR-548d-3p hsa-miR-765 hsa-miR-1266-5p hsa-miR-7706 hsa-miR-452-3p hsa-miR-452-5p hsa-miR-1254 hsa-miR-3591-5p hsa-miR-6783-3p hsa-miR-4746-5p hsa-miR-7974 hsa-miR-6844 hsa-miR-3200 -3p hsa-miR-4758 -5p hsa-miR-4664 -3p hsa-miR-3662 hsa-miR-190b hsa-miR-224-5p hsa-miR-196b-5p hsa-miR-182-5p hsa-miR-216a-5p hsa-miR-10b-5p hsa-miR-216a-3p hsa-miR-10b-3p hsa-miR-183-3p hsa-miR-135a-5p hsa-miR-216b-5p hsa-miR-96-5p hsa-miR-217 hsa-miR-183-5p hsa-miR-3144-3p hsa-miR-1269a hsa-miR-1269b hsa-miR-4652-5p hsa-miR-105-5p hsa-miR-767-5p…”